Pitfalls in the prenatal diagnosis of peroxisomal β-oxidation defects by chorionic villus sampling

Variability in the level of expression of very long chain fatty acids (VLCFAs) is documented in cultured chorionic villus (CV) cells derived from two fetuses, one at risk for an unusual peroxisomal fatty acid β-oxidation defect, and the other at risk for the X-linked form of adrenoleucodystrophy (ALD). Cells from early subcultures of chorionic cells from both cases gave normal values for VLCFA ratios. The results for the fetus at risk for the β-oxidation defect were interpreted to indicate that the fetus was not affected; however, at birth, the infant was clinically and biochemically affected. In the case of the fetus at risk for X-linked ALD, although VLCFAs were normal in subculture 1, the levels of these fatty acids increased dramatically in subculture 3, suggesting an abnormal fetus. Termination of the pregnancy and subsequent biochemical and morphological follow-up confirmed that the fetus was indeed affected by ALD.     

Prenatal detection of trisomy 21 in uncultured amniocytes by fluorescence in situ hybridization: A prospective study

A prospective study was undertaken to evaluate the use of fluorescence in situ hybridization (FISH) for the detection of trisomy 21 in interphase nuclei of uncultured amniotic fluid cells. Five hundred cases were analysed in situ and classified as normal or abnormal; the results were subsequently checked against the cytogenetic findings. Four hundred and ninety-three were correctly identified as normal with an 86·6 per cent average frequency of scored nuclei exhibiting two signals; six cases were correctly identified as trisomic for chromosome 21 with 81·7 per cent of scored nuclei exhibiting three signals; and one abnormal case involving an unbalanced chromosome 21·21 translocation was falsely scored as normal due to poor hybridization/detection efficiency. The method has been substantially improved and simplified so that it is suitable for the rapid detection of trisomy 21. As aneuploidy detection in interphase does not identify structural chromosome aberrations, it is not a substitute for fetal chromosome analysis.     

MSAFP levels and oesophageal atresia

This study was undertaken to evaluate the relationship between maternal serum alpha-fetoprotein (MSAFP) levels and oesophageal atresia (OA). OA occurred in 16 fetuses of mothers who had an MSAFP test in the study interval. The multiple of the median (MOM) value for MSAFP averaged 1·54 ± 0·65 (range 0·5–2·9 MOM), which was significantly higher than the value seen in controls. The median MOM was 1·35. Using a cut-off of 2·5 MOM, the sensitivity of MSAFP for detecting OA was 19 per cent. Although OA should be considered in the differential diagnosis of an elevated MSAFP level, MSAFP cannot be considered an appropriate screening test for OA given the low sensitivity.     

What Can Funders Do to Better Link Science with Decisions? Case Studies of Coastal Communities and Climate Change

Many reports and studies have noted that a significant portion of problem-oriented coastal science does not actually link to decisions. Here, three competitively funded project case studies are studied to determine what funders can and should do to better link science with decisions. The qualitative analysis used for this study indicates that the studied program was seen as being unusually attentive to the issue of linking science to decisions, as opposed to simply generating new knowledge. Nevertheless, much of the data indicate that funders can and should do more. Three ideas figured most prominently in the qualitative data: (1) funders should do more to ensure that the problem itself is defined more thoroughly with people who are envisioned as potential users of the science; (2) funders need to allocate more resources and attention to communicating effectively (with users) throughout the project; and (3) funders need to demand more engagement of users throughout the project. These findings have important implications for how funders review and support science, especially when competitive processes are used. Most importantly, funders should adjust what kind of science they ask for. Secondly, funders need to change who is involved in the review process. Currently, review processes focus on knowledge generation, which means that the reviewers themselves have expertise in that area. Instead, review panels should be balanced between those who focus on knowledge generation and those who focus on linking knowledge to decisions; this is a separate but critical discipline currently left out of the review process.